Alterations in the lung microbiome have been shown to be associated with several pulmonary conditions (including asthma, cystic fibrosis, and chronic obstructive pulmonary disease) and with lung transplantation. The increased rate of asthma in children has been linked to the increased rate of antibiotic use, which has a vast effect on the microbiome. Organisms in the Proteobacteria (Haemophilus, Moraxella) and Firmicutes (Streptococcus) phyla have been shown to correlate with asthma. An experimental study in mice showed an improvement in asthma when Proteobacteria organisms were replaced with Bacteriodetes organisms, which coincided with an increase in regulatory T cells and suppression of the Th2 proinflammatory cytokines prominent in the pathogenesis of asthma.
From a therapeutic standpoint, the use of probiotics to maintain a “normal” microbiome has proved useful in treating infectious diseases in the gut, and the use of probiotic therapy in patients with chronic lung infections (e.g., cystic fibrosis, upper respiratory tract infections) have been promising. The precise mechanism or mechanisms by which the bacteria may “protect” the lungs is still poorly understood but probably varies considerably according to the microorganism.
It has been shown that Bifidobacterium can activate DCs and TLRs to secrete IL-10 and retinoic acid, mediators capable of inducing regulatory T cells, which downregulate the Th2 inflammatory response. From a causative perspective, histamine, a major component of mast cell granules and secreted from Lactobacillus organisms, has been shown to have an association with priming DCs to stimulate Th2 inflammatory responses, as seen in individuals with asthma. In addition, it has been shown that ILCs can play a role in influencing the microbiome through their ability to bind to receptors on epithelial cells, thus altering the interaction of the epithelium with the microorganisms and possibly promoting colonization of either pathogenic or nonpathogenic microorganisms. Much is still to be learned and absorbed from future studies of the lung microbiome.
By far the most common pathological conditions associated with mucosal tissue are allergic responses (e.g., allergic asthma, allergic rhinitis, and food and skin allergies). Some common human allergens include components of inhaled house dust mites, cockroaches, and cat dander, as well as bee stings and ingestion of peanuts. One of the most common drug allergens is penicillin, which can bind to many endogenous proteins and also alter their antigenicity.
As previously described, the predominant antibody response in MALT is IgA; however, in an allergic response, IgE is the predominant antibody. It is generated by a switchover mechanism induced by the synthesis of IL-4 from Th2-primed CD4 T cells. The IL-4 induces the antibody-producing B cells to switch over from synthesizing IgG antibodies to IgE. IgE binds to the surface of mast cells in the submucosa through its crystallizable fragment (constant) region of the antibody molecule. Upon reexposure to the inhaled antigen and its subsequent migration from the airway lumen to the submucosa, the allergen then binds to the antigen-binding fragment region of the IgE molecule, which forms an immune complex (IgE-Ag) on the surface of the mast cell.
The final step is that IgE-Ag complexes must crosslink with other IgE-Ag complexes on the surface of the mast cell, which induce intracellular signaling pathways to initiate degranulation and immediate release of preformed Th2 mediators (histamine, heparin, prostaglandins, leukotrienes, IL-4, IL-5, IL-13, proteases). These mediators induce the classical signs of asthma: smooth muscle constriction